Document text
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
CONFIDENTIAL
Page 1BNT162b2 (COMIRNATY)
BLA STN 125742/0
Response to CBER Comment Regarding Analyses for Safety f or the Two Age Groups
August 2021
090177e197b300ac\Approved\Approved On: 02-Aug-2021 07:56 (GMT)
FDA-CBER-2021-5683-0651469
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
CONFIDENTIAL
Page 31.INTRODUCTION
Reference is made to BLA STN 125742/0 for COVID- 19 mRNA Vaccine (COMI RNATY),
for active immunization to prevent COVID -19 caused by SARS-CoV-2 in individuals
≥16years of age and to CBER’s 2 9July 2021 Information Request received via email from
Laura Gottschalk, PhD, CBER, OVRR regarding safety for the following age groups:
1)16through 55 years, 2) 56 y ears and older.
CBER’s request in bold italics is followed by Pfizer/BioNTech’s response below.
2.REQUESTS
2.1. CBER Request
Our review of the information provided in your BLA STN 125742/0 for COMIRNATY
(COVID- 19 Vaccine, mRNA), for active immunization to prevent COVID- 19 caused by
SARS-CoV-2 in individuals 16 years of age and older, is ongoing. We have the following
request for additional information:
Please submit the analyses as presented in Table 7 (page 116) of the Summary of Clinical
Safety for the following age groups: 1) 16 through 55 years, 2) 56 years and older.
Response
Table 7 in the Summary of Clinical Safety presents the incident rates of at least 1 adverse
event from dose 1 to unblinding date in the Phase 2/3 Subjects ≥ 16 Years of Age (Safety
Population). The corresponding analyses for the two requested age groups were presented
in Tables 14.106 and 14.107
located in Module 5.3.5.1 C4591001 6-Month Update Interim
CSR Section 14, which are also provided in this response
(Table 1 and Table 2).
090177e197b300ac\Approved\Approved On: 02-Aug-2021 07:56 (GMT)
FDA-CBER-2021-5683-0651471
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
CONFIDENTIAL
Page 4Table 1. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date, by Age Group –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: 16- 55 Years
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=12995, TEb=49.7)Placebo
(Na=13026, TEb=49.1)
Adverse Event ncIR (/100PY)d(95% CIe) ncIR (/100PY)d(95% CIe)
Any event 4396 88.4 (85.8,91.0) 2136 43.5 (41.7,45.4)
Relatedf3484 70.0 (67.7,72.4) 884 18.0 (16.8,19.2)
Severe 193 3.9 (3.4,4.5) 124 2.5 (2.1,3.0)
Life-threatening 13 0.3 (0.1,0.4) 20 0.4 (0.2,0.6)
Any serious adverse event 103 2.1 (1.7,2.5) 117 2.4 (2.0,2.9)
Relatedf3 0.1 (0.0,0.2) 1 0.0 (0.0,0.1)
Severe 56 1.1 (0.9,1.5) 75 1.5 (1.2,1.9)
Life-threatening 13 0.3 (0.1,0.4) 20 0.4 (0.2,0.6)
Any adverse event leading to
withdrawal22 0.4 (0.3,0.7) 28 0.6 (0.4,0.8)
Relatedf9 0.2 (0.1,0.3) 8 0.2 (0.1,0.3)
Severe 5 0.1 (0.0,0.2) 6 0.1 (0.0,0.3)
Life-threatening 3 0.1 (0.0,0.2) 5 0.1 (0.0,0.2)
Death 3 0.1 (0.0,0.2) 4 0.1 (0.0,0.2)
a. N = number of subjects in the specified group.
b. TE= total exposure time in 100 person -years across all subjects in the specified group. Exposure time for a subject is the time from Dose 1 to the end
of blinded follow -up. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of subjects reportin g at least 1
occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total expo sure time in 100 person -years (PY) across all subjects in the
specified group.
e. 2-sided CI based on Poisson distribution.
f. Assessed by the investigator as related to investigational product.
090177e197b300ac\Approved\Approved On: 02-Aug-2021 07:56 (GMT)
FDA-CBER-2021-5683-0651472
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
CONFIDENTIAL
Page 5Table 1. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date, by Age Group –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: 16- 55 Years
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=12995, TEb=49.7)Placebo
(Na=13026, TEb=49.1)
Adverse Event ncIR (/100PY)d(95% CIe) ncIR (/100PY)d(95% CIe)
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021 (02:10)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File: ./nda2_unblinded/C4591001_BLA/adae_s092_unb_age_p3_saf
Table2.Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date, by Age Group –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: >55 Years
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=8931, TEb=33.7)Placebo
(Na=8895, TEb=33.1)
Adverse Event ncIR (/100PY)d(95% CIe) ncIR (/100PY)d(95% CIe)
Any event 2551 75.7 (72.8,78.7) 1432 43.3 (41.1,45.6)
Relatedf1762 52.3 (49.9,54.8) 429 13.0 (11.8,14.3)
Severe 163 4.8 (4.1,5.6) 132 4.0 (3.3,4.7)
Life-threatening 35 1.0 (0.7,1.4) 34 1.0 (0.7,1.4)
Any serious adverse event 165 4.9 (4.2,5.7) 151 4.6 (3.9,5.4)
Relatedf1 0.0 (0.0,0.2) 0 0.0 (0.0,0.1)
Severe 92 2.7 (2.2,3.3) 81 2.4 (1.9,3.0)
090177e197b300ac\Approved\Approved On: 02-Aug-2021 07:56 (GMT)
FDA-CBER-2021-5683-0651473
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
CONFIDENTIAL
Page 6Table2.Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date, by Age Group –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: >55 Years
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=8931, TEb=33.7)Placebo
(Na=8895, TEb=33.1)
Adverse Event ncIR (/100PY)d(95% CIe) ncIR (/100PY)d(95% CIe)
Life-threatening 35 1.0 (0.7,1.4) 34 1.0 (0.7,1.4)
Any adverse event leading to
withdrawal23 0.7 (0.4,1.0) 23 0.7 (0.4,1.0)
Relatedf4 0.1 (0.0,0.3) 4 0.1 (0.0,0.3)
Severe 5 0.1 (0.0,0.3) 6 0.2 (0.1,0.4)
Life-threatening 12 0.4 (0.2,0.6) 11 0.3 (0.2,0.6)
Death 12 0.4 (0.2,0.6) 10 0.3 (0.1,0.6)
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person -years across all subjects in the specified group. Exposure time for a subject is the time from Dose 1 to the end of
blinded follow -up. This value is the denominator fo r the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of subjec ts reporting at least 1
occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person -years (PY) across all subjects in the specified
group.
e. 2-sided CI based on Poisson distribution.
f. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021 (02:10)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File: ./nda2_unblinded/C4591001_BLA/adae_s092_unb_age_p3_saf
090177e197b300ac\Approved\Approved On: 02-Aug-2021 07:56 (GMT)
FDA-CBER-2021-5683-0651474
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 73.REFERENCES
None
090177e197b300ac\Approved\Approved On: 02-Aug-2021 07:56 (GMT)
FDA-CBER-2021-5683-0651475